Effects of nutritional therapy on chemiluminescence in Crohn's disease.
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Biomedical subjects
Publications and source records attributed to N Okabe.
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The interaction between 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3-methoxytyramine and homovanillic acid and bovine serum albumin (BSA) was investigated by the ultrafiltration technique. The apparent binding constants were determined assuming the equivalence and independence of the binding sites on the BSA molecule. The binding constants were in the range of log K = 2.85 to 3.77 with 1 to 2 binding sites. The affinity of ligands to BSA strengthened with progression of the metabolism in the order of DOPA less than dopamine less than 3-methoxytyramine less than homovanillic acid.
The TD97 strain vaccine virus was prepared from the Tanabe strain measles virus by low-temperature passages in primary cell cultures and ultraviolet (UV) mutagenesis. The TD97 strain exhibited the following characteristics: highly temperature sensitive, neither multiplying nor forming any plaques at 40 degrees C in Vero cells; genetically stable, maintaining high temperature sensitivity after ten successive passages in CE cells at 30 degrees C or 35 degrees C; and M proteins of this virus about 1 KD slower in mobility in SDS-PAGE than that of the Tanabe strain. The TD97 strain was further confirmed to be attenuated by an inoculation test into primate brain. In field trials, 752 healthy children were inoculated with a live virus vaccine prepared with this strain, and the following results were obtained: the seroconversion rate was 97% (517/533), and the average HI antibody titer was 2(5.2). An antibody-increasing effect was also observed in children who were initially seropositive. In children who seroconverted, the rates of fever were 15.7% (55/351) for 37.5 degrees C or higher and 4.0% (14/351) for 39 degrees C or higher. The rash rate was 7.7% (27/351), and the incidence of local reaction was 5.4% (19/351). The TD97 strain is thus considered to be suitable in use for an attenuated measles vaccine.
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Synthetic analogues of retinoic acid, isotretinoin in particular, are known to cause granulation tissue in the nail sulcus and healing cystic acne. We observed granulation tissue that developed in a psoriatic patient on long-term oral etretinate therapy (30 mg/day for 3 years), another synthetic analogue of retinoic acid. In August of 1988, the patient, a 44-year-old male, hit his lower leg against a wooden stick, resulting in a laceration. At that time he had relatively limited patches of psoriasis, but his skin was generally thin with telangiectasia, even in areas without psoriasis, probably due to the long-term use of oral etretinate and topical steroid. In spite of treatment with topical disinfectants and oral antibiotics, the wound progressed into granulation tissue surrounded by erythema and multiple punctate erosions with marked secretion of a clear exudate. The histological findings of the granulation tissue included the presence of proliferating microvessels and a relatively dense cell infiltration with a predominance of plasma cells on the sparse edematous connective tissue. Based on these findings, the rash was considered to be retinoid-induced granulation tissue. As compared with previous reports, our case had the following characteristics: development of rash after minor trauma, rash on the lower leg, eosinophil infiltration into the rash. We believe that long-term users of oral etretinate should be cautioned about the potential for delayed wound healing and the formation of granulation tissue.
We have been examining superoxide production activity in patients with Crohn's disease and we noted an increase in this activity in peripheral whole blood and monocytes, determined by a luminol-dependent chemiluminescence. However, superoxide production and phagocytosis are different phenomena. To search for the "real" phagocytic capacity, we examined the phagocytic activity of peripheral blood monocytes and neutrophils in 20 Japanese patients with Crohn's disease, using automated laser flow cytometry. In contrast to the results obtained with the chemiluminescence assay, we found a decrease in the "real" phagocytic function in monocytes, yet there was no difference in the phagocytic ability in neutrophils. The phagocytic activity in patients with an active form of the disease was lower than that in patients with inactive form of the disease. These results provide pertinent information on the role of monocytes in Crohn's disease. The depressed phagocytic activity in monocytes from these patients may play some role in the pathogenesis of this disease.
The interaction between a major thyroid hormone metabolite, 3,3',5'-triiodo-L-thyronine and bovine serum albumin was investigated by fluorescence measurements. The apparent binding constants were obtained at various pHs assuming the equivalence and independence of the interaction sites on the protein from the fluorescence titration curves. The maximum binding was attained at pH 8.0, and the apparent binding constant was (5.28 +/- 0.13).10(5) M-1 with one binding site per albumin molecule. Thermodynamic parameters were also determined from the van't Hoff plot of the apparent binding constants at pH 7.5. The free energy change, enthalpy change and entropy change were -7.70 +/- 0.09 kcal.mol-1, -4.59 kcal.mol-1 and 10.2 e.u., respectively.
In three cases a nasalis musculocutaneous flap, using the dog-ear, has been used to help close the secondary defect after transfer of a superiorly based nasolabial flap to the nose. In one case part of the nasalis flap was used to close a defect in the nasal lining.
The nuclear thyroid hormone binding protein (NTHB) with the molecular weight of 57 kDa was obtained from rat liver nuclear extracts by using HPLC and DEAE-Sephadex A-25 ion exchange chromatography methods. Fluorescein isothiocyanate-labeled 3,5,3'-triiodo-L-thyronine (F-T3) was used as a fluorescent probe to identify the hormone binding protein. Purified NTHB has a single binding site for T3 with the apparent binding constant of (3.3 +/- 0.7) X 10(8) M-1. NTHB is an acidic protein with a pI of 5.0. The secondary structure of NTHB is characterized by about 42% helical and 18% beta-structure from CD measurements.
We studied the differences in oxygen metabolite generation, using a chemiluminescence (CL) assay, in peripheral blood phagocytic cells from various donors including healthy young volunteers, patients with acute or chronic inflammation, pregnant women, and elderly persons. The CL response of polymorphonuclear leukocytes (PMN) after stimulation with serum-opsonized zymosan was increased in patients with acute inflammation due to infection and in pregnant women as compared with that in controls. Monocytes from those patients also showed a slight increase of the CL response. In contrast, CL of monocytes from patients with chronic inflammation (Crohn's disease patients) and elderly persons was significantly enhanced, whereas that of their PMN remained in the range of control values. The significance of these results was discussed.
A conventional limulus test can detect not only endotoxin but also beta(1----3) glucan. Therefore, with a quantitative limulus test, the limulus colorimetric test, we studied the pharmacokinetics of lentinan, an antitumor beta(1----3) glucan preparation, in the blood of 10 healthy volunteers and 20 patients with advanced cancers. The calibration curve of lentinan in the human plasma was linear in the range of 0 to 100 ng/ml. Two mg of lentinan was administered once a week and blood samplings for the measurement were done immediately before the next lentinan administration to document trough-levels serially at a week interval. Trough-levels tended to rise gradually and showed a rapid elevation between 4 and 8 weeks after beginning of administration. This phenomenon may correlate closely with the antitumor effect of lentinan and, therefore, deserves further investigations.
We attempted to clarify the association between HLA and Crohn's disease. HLA-A, -B, -C, -DR and -DQ locus antigens in 108 Japanese patients with Crohn's disease were analyzed and the results were compared with findings of 472 healthy Japanese. In patients with Crohn's disease there was a strong positive association with HLA-DR4 (chi 2 = 14.086, Pc less than 0.005, RR = 2.231), and a weak positive association with HLA-B51, -Bw54, -DRw12, -DRw13 and -DRw52. While there was a strong negative association with HLA-DR2 (chi 2 = 10.194, Pc less than 0.025, RR = 0.435), DQw1 (chi 2 = 14.680, Pc less than 0.001 RR = 0.442) and DQw3 (chi 2 = 7.760 Pc less than 0.025 RR = 0.549), and a weak negative association with HLA-B7. In conclusion, susceptibility to Crohn's disease may relate to HLA-DR4, especially HLA-DR4.1, in Japanese patients.
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A multiclinic study of gentamicin (GM) given by intravenous drip infusion was carried out by the Gentamicin Pediatric Study Group. The results are summarized as follows: 1. Upon intravenous drip infusion of GM at a dose range of 2.0-2.5 mg/kg over a period of 0.5-1 hour, therapeutically effective serum concentrations of 4-12 micrograms/ml were obtained. These values are similar to reported values in previous studies using GM intramuscular injection. 2. High urinary concentrations were observed up to 6 hours after administration, and the urinary recovery rate was approximately 60%. 3. Of a total of 142 cases collected, 117 cases were evaluated. Efficacy rates by diseases were: 100% in pneumonia (30/30), 98.3% in urinary tract infections (59/60), and 92.3% in other infections (skin and soft tissue) (12/13), with an overall efficacy rate of 94.9% (including 77 "excellent" cases). 4. Bacteriological examinations showed high eradication rates with the use of GM; i.e., 80% with Staphylococcus aureus (8/10), 60% with Pseudomonas aeruginosa (3/5), 100% with Haemophilus influenzae (7/7) and 97.8% with Escherichia coli (44/45), achieving an overall eradication rate of 92.4%. In mixed infections, the eradication rate was 85.7% (6/7). 5. No ototoxicity, nephrotoxicity or allergic reactions was observed. Abnormal laboratory findings observed were: GOT elevation in 3.1% of cases, GPT elevation in 3.9%, platelet increase in 1.5% and eosinophil increase in 0.8%, thus an overall rate of the appearance of abnormality was 5.6%. The above results indicate that an intravenous drip infusion of GM is a useful method for treating infections in pediatrics.
Studies done in our laboratories showed that monocytes in Crohn's disease (CD) have an increased phagocytic activity determined using chemiluminescence assay. To further elucidate the pathogenesis of CD, we studied the monokine production activity and the proportion of HLA-DR(+) monocytes in the peripheral blood of 16 Japanese with CD. In contrast to the phagocytic function, an impaired monokine production activity and a decreased percentage of DR(+) monocytes were evident. The number of DR(+) monocytes showed a negative correlation to CRP. These findings provide additional information on the monocyte function in CD and indicate that monocyte dysfunction may be closely linked to the pathogenesis of CD.
The total number of circulating leucocytes in the peripheral blood of pregnant women progressively increased with advance in gestation because of neutrophilia. When the phagocytic activity, representing nonspecific immunity, was estimated by a luminol-dependent chemiluminescence (CL) response during phagocytosing opsonized zymosan, we observed that the CL response of whole blood and Ficoll-Paque separated polymorphonuclear leucocytes (PMNL) significantly increased throughout the pregnancy (P less than 0.01). The CL responses of mononuclear leucocytes (MN) and monocytes also increased and reached peak levels in the third trimester (P less than 0.05). These findings suggest that the phagocytic activity in pregnant women increases, not only with regard to the number of phagocytes but also with regard to individual cell function, from a relatively early stage of the pregnancy, and that this increased nonspecific immunity may compensate in part for a weakened specific immunity of the maternal host. Attention should be directed to effects of human chorionic gonadotropin (hCG) relative to the increased CL response during pregnancy.